The derivatives of functionalized pyrrolidines are structural components of many bioactive natural products and pharmaceutically important substances. In particular, anisomycin is a basic antibiotic, while domoic acid and kainic acid are potent neuroexcitatory amino acids.
EP 0132580 A1 reports a process for the preparation of a compound of formula I,
in which R is hydrogen, (C1-C6) alkyl or (C7-C9) aralkyl group, and R1 to R6 are identical or different and are independently hydrogen, (C1-C8)-alkyl, (C3-C9)-cycloalkyl, (C3-C9) cycloalkyl (C1-C4) alkyl, (C5-C9) cycloalkenyl (C1-C4) alkyl, (C6-C12)-aryl-(C1-C4) alkyl or (C6-C12)-aryl, in each case both in the aryl moiety by (C1-C4)-alkyl, (C1-C4) alkoxy, hydroxy, halogen, nitro, methylenedioxy and/or cyano, mono-, di- or tri-substituted can be mean, or in which two of the radicals R to R6, together with the carbon atom carrying or: with the two carrying them, carbon atoms, a 4- to 10-membered saturated or unsaturated mono- or bicyclic carbocyclic ring system and the other radicals are hydrogen, characterized in that a pyrrolidine derivative of the formula II,
in which R1 to R6 have the same meaning as in formula I, with an oxidizing agent in the presence of a silver salt in a Δ1-Pyrrolinderivat of the formula III,
in which R and R6 have the same meaning as in formula I, transferred, this, with hydrogen cyanide or a metal cyanide to give a compound of the formula IV,
in which R1 to R6 have the same meaning as in formula I, is reacted, and with a compound of the formula ROH in which R has the meaning defined above, are reacted to form a compound of the formula I.U.S. Pat. No. 4,988,710 reports
wherein R1 is one or more groups independently selected from hydrido, halo, alkyl, acyl, hydroxyalkyl, haloalkyl, aminoalkyl, alkoxy, amino, alkylamino and acylamino; wherein R2 is selected from hydrido, cycloalkyl, cycloalkenyl, halocycloalkyl, alkylcycloalkyl, acylcycloalkyl, hydroxycycloalkyl, haloalkylcycloalkyl, aminoalkylcycloalkyl, alkoxycyclo-alkyl, aminocycloalkyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl wherein the tricycloalkyl, bicyclo-alkenyl and tricycloalkyl groups may be substituted with one or more groups selected from alkyl, halo, acyl, hydroxy, hydroxyalkyl, haloalkyl, acyl, alkoxy, amino and alkylamino; wherein each of R3 and R4 is independently selected from hydrido, alkyl, acyl, alkenyl, cycloalkyl, phenylalkyl, phenyl, aminoalkyl and alkylaminoalkyl; and wherein R3 and R4 may be taken together to form a cyclic group including the nitrogen atom of Formula I, and n is an integer selected from one through five.
Article titled, “1,3-Dipolar Cycloaddition of Hydrazones with α-Oxo-ketenes: A Three-Component Stereoselective Entry to Pyrazolidinones and an Original Class of Spirooxindoles” by Marc Presset; Kishor Mohanan; Marie Hamann; Yoann Coquerrel; Jean Rodriguez. in Org. Lett. 2011, 13, 4124 reports stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3-ones efficient preparation by a three-component reaction involving a 1,3-dipolar cycloaddition of azomethine imines obtained from hydrazones with α-oxo-ketene dipolarophiles generated in situ, with excellent diastereoselectivity in a single catalyst/additive-free, highly economic transformation.
Article titled, “Organocatalytic Sequential α-Amination/Corey-Chaykovsky Reaction of Aldehydes: A High Yield Synthesis of 4-Hydroxypyrazolidine Derivatives” by B. Senthil Kumar; V. Venkatramasubramanian; Arumugam Sudalai. in Org. Lett. 2012, 14, 2468 reports a tandem reaction of in situ generated α-amino aldehydes with dimethyloxo sulfonium. methylide under Corey-Chaykovsky reaction conditions proceeds efficiently to give 4-hydroxypyrazolidine derivatives in high yields with excellent enantio- and diastereoselectivity. This organocatalytic sequential method provides for the efficient synthesis of anti-1, 2-aminoalcohols, structural subunits present in several bioactive molecules as well.
Above methods involve drawbacks of multistep processes, complex starting materials, expensive as well as toxic transition metal catalysis, poor enantio and diastereoselectivity. Our method overcomes these shortages through very good enantio and diastereoselectivity with good yields in a one-pot process via organocatalysis.
Due to their biological importance and structural complexity, easy and efficient method of construction of pyrrolidine units is the need of time.